The main aims of this project are (1) to further develop and test a chick learning system for behavioral-pharmacological-neurochemical studies of effects and mechanisms of opioids, and (2) to use this system to elucidate actions of opioids in the CNS in relation to learning and memory in order to increase understanding of the mechanisms of drug abuse and of effects of opioid drugs on cognition and behavior. Specific lines of research to be undertaken with the chick system include the following: (1) test agonists and antagonists selective for the three main classes of opioid receptor for memory-enhancing and amnestic effectiveness when injected either at certain brain sites or peripherally, and investigate which stage(s) of memory formation (short-, intermediate-, or long-term memory) are affected by these agents; (2) determine whether the metabolites of opioids influence learning and memory in the chick; (3) test effects of opioid agonists and antagonists in modulating the role of the cholinergic system on learning and memory in the chick to better understand how opioids affect memory with other neurotransmitter systems; and (4) extend the analyses of opioid degrading enzyme activity of chick brain to smaller functionally distinct areas, using high performance liquid chromatography with electrochemical detection (HPLC-ECD) and measure the concentrations of opioids in the same brain areas using radioimmunoassays (RIA) to compare the resulting map to that of opioid degrading enzyme activity. This project is based on a combination of methods and expertise of the PI's with one-trial learning in neonate chicks, opioids and opioid systems in behavioral experiments, and neurochemical techniques to study mechanisms of memory formation and of opioid effects.